Suppression of TRPV5 Regulates Microglia-Mediated Neuroinflammation Following Status Epilepticus

Abstract

Neuroinflammation, predominantly associated with glial activation and the release of various inflammatory mediators, is a vital hallmark of the pathophysiology of epilepsy. Numerous studies have indicated that identifying novel factors that diminish neuroinflammatory processes may be important for developing effective therapeutic strategies to prevent neuropathological processes and epileptogenic progression. Transient receptor potential vanilloid 5 (TRPV5) is a highly selective calcium ion channel belonging to the TRPV family. TRPV5 expression has been identified in diverse regions of the brain; however, it remains unknown how TRPV5 is implicated in the pathophysiological features of neurological diseases, including epilepsy. Herein, we show that TRPV5 expression is upregulated in the hippocampus of a pilocarpine-induced status epilepticus (PCSE) model, predominantly in activated microglia. Pharmacological inhibition of TRPV5 using econazole attenuated microglial activation, as indicated by the shift of LPS-stimulated primary hippocampal microglia to a resting state. This inhibition suppressed AKT/NF-kappa B signaling, reduced NLRP3 inflammasome activity, and decreased proinflammatory cytokine production. Additionally, TRPV5 inhibition reduced hippocampal microglial activation and neuroinflammation following PCSE. These findings suggest that TRPV5 contributes to the regulation of microglial activation, resulting in the suppression of microglia-derived neuroinflammation during the sub-acute phase of epilepsy. In conclusion, the present study suggests that targeting TRPV5 may offer a novel therapeutic approach to managing the neuroinflammatory processes during epileptogenic progression.